Endocrinology/Objectives/Lecture 17
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Objectives: 13 - 14 - 15 - 16 - 17 - 18 - 19 - 20 - 21 - 22 - 23 - 24 - 25
Endocrinology of the pancreas
List the cell types of the islets of Langerhans and the hormones they produce.
| Cell type | Hormone produced | Location within islet |
|---|---|---|
| α (A) cell | Glucagon | Periphery |
| β (B) cell | Insulin | Center (receives blood supply first) |
| δ (D) cell | Somatostatin | Periphery |
Describe the physiologic action of insulin and glucagon on the liver, adipose tissue, adrenal glands, and pancreatic islets.
| Hormone | Tissue | Actions |
|---|---|---|
| Insulin | Liver |
|
| Adipose tissue |
| |
| Adrenal glands |
| |
| Pancreatic islets |
| |
| Muscle |
| |
| Glucagon | Liver |
|
| Adipose tissue |
| |
| Adrenal glands |
| |
| Pancreatic islets |
| |
| Muscle |
|
Describe a possible role of somatostatin on islet cell function.
Somatostatin, a 28-amino acid peptide hormone, may be released by δ cells in reponse to glucagon and may act to suppress the secretion of both glucagon and insulin.
Describe the regulation of glucagon and somatostatin secretion.
Glucagon secretion is inhibited by both insulin and somatostatin, and is stimulated by α-adrenergic input (e.g. by norepinephrine from sympathetic outflow). Somatostatin secretion is stimulated by glucagon.
Explain how glucagon and somatostatin are involved in the regulation of blood glucose levels.
Glucagon is released during fasting states and stimulates glycogenolysis, protein breakdown, gluconeogenesis, lipolysis, and ketogenesis. It serves to maintain blood glucose levels between meals.
Somatostatin may be released in response to glucagon secretion and may participate in the inhibition of insulin secretion between meals.
List the major controls regulating insulin secretion.
- Blood glucose levels
- Adrenergic input
- α-Adrenergic input (e.g. via sympathetic outflow, norepinephrine) is inhibitory
- β-Adrenergic input (e.g. isoproterenol) is stimulatory
- Cholinergic input (e.g. via parasympathetic outflow) is stimulatory
- Somatostatin may inhibit insulin release
Describe the effects of feeding and of fasting on insulin secretion.
- Feeding →
- ↑Blood glucose → ↑insulin
- ↑Parasympathetic outflow → ↑pancreatic cholinergic input → ↑insulin
- Fasting →
- ↓Blood glucose → ↓insulin
- ↓Insulin → ↑glucagon → ↑somatostatin → ↓insulin
Predict the effect of decreased plasma glucose, amino acids, and free fatty acids on secretion of various substances
| Hormone | Effect |
|---|---|
| Cortical steroids | ↑ |
| Growth hormone | ↑ |
| Glucagon | ↓glucose → ↑glucagon ↓amino acids → ↓glucagon |
| Somatostatin | ↑ |
| Catecholamines | ↑ |
Describe the sequence of events which leads to hemoconcentration, metabolic acidosis, and electrolyte loss from the body after total pancreatectomy.
- ↓Insulin → ↓K+ uptake → ↓renin-angiotensin system → ↓aldosterone →
- ↓blood volume → hemoconcentration
- ↓H+ excretion → metabolic acidosis
- ↓Blood volume → ↓blood pressure → renal failure → electrolyte loss
Describe the relationships between total body fat and glucose tolerance, and total body fat and the response to a given amount of insulin in humans. Suggest a mechanism to account for these relationships.
Body fat increases with frequent eating (obesity), which also results in high blood glucose and constitutive secretion of insulin. Chronically high insulin levels lead to insulin resistance to the point that even the excessively high levels of insulin are incapable of stimulating glucose uptake by cells (i.e. insulin-resistant individuals are glucose-intolerant). An insulin-resistant individual will have very little response to an insulin challenge; after all, insulin-resistant individuals already have incredibly high levels of circulating insulin.
Insulin resistance may be caused by downregulation of insulin receptors, a process which may occur with chronically elevated insulin levels.
Explain what is meant by downregulation of insulin receptors and its relationship to plasma insulin levels.
Insulin receptor downregulation is the process by which insulin receptors are removed from the plasma membrane, resulting in a cell that is less sensitive to insulin. Insulin receptors are downregulated in the presence of chronic ligand (i.e. insulin) just as most other receptors (e.g. β-adrenergic receptors) are. Receptors are endocytosed and stored in cytoplasmic vesicles or inactivated by hydrolysis.
Compare and contrast type I and type II diabetes mellitus.
Type I diabetes mellitus is insulin-dependent and may result from autoantibodies directed against β cells of the pancreatic islets. Type II diabetes mellitus is non-insulin-dependent and results from insulin resistance, the mechanism for which is discussed above. The pathophysiology of both diseases begins with excess plasma glucose, which results in the glycosylation of various proteins (e.g. proteins of the eye, causing glaucoma; HbA1C, resulting in poorly deformably erythrocytes and anoxia). The diseases differ in that type II diabetics are sensitive enough to insulin to allow enough glucose uptake to keep the rate of ketogenesis relatively low. Type I diabetics require ketogenesis to stay alive, and the resulting production of ketoacids (e.g. β-hydroxybutyric acid and acetoacetic acid) results in life-threatening metabolic acidosis that is fatal if not properly treated.
